Intermittent acute prophyria (IAP) is a dominantly inherited disorder of porphyrin biogenesis characterized clinically by neuropsychiatric dysfunction. The recent discovery of the primary biochemical-genetic defect in IAP - a deficiency of uroporphyrinogen-I-synthetase activity in most tissues - prompted the development in this laboratory of a rapid, simple, highly specific and sensitive spot test for the deficiency of this enzyme. The present proposal is to apply this spot test to a population of patients who have been hospitalized because of mental illness of all types, to determine whether the prevalence of IAP constitutes significant causative factor thereof. The screening test will be performed on blood collected from about 8,000 in-patients of two local psychiatric hospitals. By way of control, screening will also be carried out on samples from about 15,600 patients at a local ambulatory health facility. Individuals with normal concentrations of this erythrocyte enzyme can be readily identified by means of this spot test. For individuals whose screening test suggests enzyme deficiency, a second blood sample, collected specifically for quantitative analysis of uroporphyrinogen-I-synthetase, will be obtained. A deficiency of the enzyme by this quantitative analysis will confirm the diagnosis of IAP. The psychiatric characteristics of the affected individuals ascertained through this survey will be studied, to determine whether any unique syndrome is operative. The finding through this survey of an appreciable prevalence of IAP in this population will provide impetus to further biochemical research on the pathogenesis of mental illness, and will in addition provide a population of individuals in whom to test newer modes of treatment of IAP.